Alpha7 cholinergic-agonist prevents systemic inflammation and improves survival during resuscitation.
Alpha7 cholinergic-agonist prevents systemic inflammation and improves survival during resuscitation.
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DOI：
10.1111/j.1582-4934.2008.00550.x
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发表时间：
2009-09
影响因子：
5.3
通讯作者：
Ulloa L
中科院分区：
文献类型：
--
作者：
Cai B;Chen F;Ji Y;Kiss L;de Jonge WJ;Conejero-Goldberg C;Szabo C;Deitch EA;Ulloa L
尽管最近在重症监护方面取得了进展，但严重出血仍是导致死亡的常见原因。传统的复苏液体旨在重建组织灌注，但它们无法防止复苏期间的炎症反应。我们之前的研究表明迷走神经可以通过α7烟碱乙酰胆碱受体（α7nAchR）调节全身性炎症。在这里，我们报告了alpha7nachr激动剂GTS，可以抑制全身炎症并提高复苏期间的生存率。GTS复苏使所有动物免于致死性出血，并呈浓度依赖性。与传统的复苏液不同，GTS抑制特征性炎症和心脏抑制因子的产生，包括肿瘤坏死因子（TNF）和高迁移率B组蛋白-1 （HMGB1）。GTS复苏在抑制全身TNF反应和抑制其在脾脏中的产生方面特别有效。在分子水平上，GTS在复苏过程中抑制p65RelA，而不抑制RelB NF-κB。与非特异性尼古丁激动剂不同，GTS在正常和脾切除出血动物中均能抑制血清蛋白TNF水平。GTS复苏抑制多聚腺苷核糖（adp -核糖）聚合酶和全身HMGB1水平。我们的研究表明，与非特异性烟碱激动剂相比，GTS具有显著的优势，它可能是一种有希望的抗炎补充剂，可以提高复苏期间的生存率。
Severe haemorrhage is a common cause of death despite the recent advances in critical care. Conventional resuscitation fluids are designed to re-establish tissue perfusion, but they fail to prevent inflammatory responses during resuscitation. Our previous studies indicated that the vagus nerve can modulate systemic inflammation via the alpha7 nicotinic acetylcholine receptor (α7nAchR). Here, we report that the alpha7nAChR-agonist, GTS, restrains systemic inflammation and improves survival during resuscitation. Resuscitation with GTS rescued all the animals from lethal haemorrhage in a concentration-dependent manner. Unlike conventional resuscitation fluids, GTS inhibited the production of characteristic inflammatory and cardiodepressant factors including tumour necrosis factor (TNF) and high mobility group B protein-1 (HMGB1). Resuscitation with GTS was particularly effective in restraining systemic TNF responses and inhibiting its production in the spleen. At the molecular level, GTS inhibited p65RelA but not RelB NF-κB during resuscitation. Unlike non-specific nicotinic agonists, GTS inhibited serum protein TNF levels in both normal and splenectomized, haemorrhagic animals. Resuscitation with GTS inhibited poly(ADP-ribose) polymerase and systemic HMGB1 levels. Our studies suggest that GTS provides significant advantages as compared with non-specific nicotinic agonists, and it could be a promising anti-inflammatory supplement to improve survival during resuscitation.
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影响因子：
29.4
作者：
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